The objective of the proposed research is to determine the effectiveness of cough for enhancing clearance of mucus from the lung in both health and disease. The efficiency of cough for both central and peripheral airway clearance will be analyzed. First, in healthy individuals with normal lung function, the efficiency of cough will be compared between groups of nonsmokers and smokers. Following these studies, the effectiveness of cough in individuals with chronic obstructive pulmonary disease (COPD) will be studied. Because recent studies indicate that chronic flow-limitation (i.e. tidal breathing superimposed on maximal expiratory flow volume loop) may affect mucociliary clearance, the analysis of coughing in COPD will compare subjects who are chronically flow-limited to those who are not. Finally, based on theoretical models of cough which define the parameters important in maximizing cough efficiency, a number of therapeutic manipulations of cough efficiency will be analyzed in subjects with COPD. These manipulations may include a) coughing with a denser gas mixture (SF6-02), b) use of beta-adrenergic agents, c) use of mucolytic agents, and d) water vapor inhalation. The efficiency of cough in these studies will be determined by measuring the clearance of radiolabelled (Tc 99m), monodisperse aerosols from the lung using a gamma camera interfaced with a computer. In each subject, the clearance of these particles will be measured on a control and cough study. On the cough study day subjects will perform sixty (60) controlled coughs during the first hour of clearance following deposition of the particles. Particle sizes and breathing patterns will be carefully controlled to insure that lung deposition patterns are matched between control and cough study days. Coughing efficiency on central and peripheral airway clearance will be studied in separate groups of subjects by changing particle sizes and breathing patterns to produce either predominantly central or peripheral airway deposition. Furthermore, an attempt will be made to match these deposition patterns (either central or peripheral) between different groups of subjects studied (e.g. nonsmokers, smokers, COPD flow-limited and nonflow-limited subjects). Then, the relative efficiency of cough can be compared between the various groups studied. The results of these studies should provide information on the factors that determine coughing efficiency in health and disease.